Wound pH-Responsive Sustained Release of Therapeutics from a Poly(NIPAAm-co-AAc) Hydrogel
13 Apr 2012-Journal of Biomaterials Science-polymer Edition (Taylor & Francis Group)-Vol. 23, pp 111-132
TL;DR: A poly(N-isopropylacrylamide-co-acrylic acid) hydrogel was evaluated as pH-sensitive sustained release system for wound-pH-dependent therapeutics delivery and showed augmentation of wound healing in comparison to conventional sustained release growth factor therapy.
Abstract: Wound pH strongly influences residence time and activity of various growth factors during wound healing. Hence, a pH-responsive sustained release growth factor delivery system could be beneficial for effective treatment of wound. In this context, an effort was made to evaluate the potential of a poly(N-isopropylacrylamide-co-acrylic acid) hydrogel as pH-sensitive sustained release system for wound-pH-dependent therapeutics delivery. The polymer was synthesized via radical copolymerization and influence of pH on lower critical solution temperature (LCST), microarchitechture and swelling of the hydrogel was evaluated. Results showed a pH-dependent variation in the physical properties of the hydrogel within the wound pH range. Fluorescence recovery after photobleaching (FRAP) analysis endorsed a pH dependent restricted diffusion of the BSA in the hydrogel. Later, release of bovine serum albumin (BSA), vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) (each 5%, w/v) from the hydrogel...
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TL;DR: The fabrication of novel carboxylated agarose/tannic acid hydrogel scaffolds cross-linked with zinc ions for the pH-controlled release of tannic acids display cytocompatibility, antibacterial, and anti-inflammatory characteristics that make them promising candidates for wound dressings.
Abstract: pH-sensitive hydrogels play an important role in controlled drug release applications and have the potential to impact the management of wounds. In this study, we report the fabrication of novel carboxylated agarose/tannic acid hydrogel scaffolds cross-linked with zinc ions for the pH-controlled release of tannic acid. The resulting hydrogels exhibited negligible release of tannic acid at neutral and alkaline pH and sustained release at acidic pH, where they also displayed maximum swelling. The hydrogels also displayed favorable antibacterial and anti-inflammatory properties, and a lack of cytotoxicity toward 3T3 fibroblast cell lines. In simulated wound assays, significantly greater cell migration and proliferation was observed for cells exposed to tannic acid hydrogel extracts. In addition, the tannic acid hydrogels were able to suppress NO production in stimulated human macrophages in a concentration-dependent manner, indicating effective anti-inflammatory activity. Taken together, the cytocompatibilit...
402 citations
TL;DR: The objective of this review is to concisely describe the relevance of hydrogel dressings as platforms for delivery of active molecules for improved management of difficult- to-treat wounds.
Abstract: Background Composed in a large extent of water and due to their nonadhesiveness, hydrogels found their way to the wound dressing market as materials that provide a moisture environment for healing while being comfortable to the patient Hydrogels' exploitation is constantly increasing after evidences of their even broader therapeutic potential due to resemblance to dermal tissue and ability to induce partial skin regeneration The innovation in advanced wound care is further directed to the development of so-called active dressings, where hydrogels are combined with components that enhance the primary purpose of providing a beneficial environment for wound healing Objective The objective of this review is to concisely describe the relevance of hydrogel dressings as platforms for delivery of active molecules for improved management of difficult- to-treat wounds The emphasis is on the most recent advances in development of stimuli- responsive hydrogels, which allow for control over wound healing efficiency in response to different external modalities Novel strategies for monitoring of the wound status and healing progress based on incorporation of sensor molecules into the hydrogel platforms are also discussed
143 citations
TL;DR: Methods to determine drug diffusion coefficients and in vitro and in vivo models used to assess drug release and efficacy are reviewed to provide guidelines and harmonized practices when investigating novel hydrogel drug delivery systems.
Abstract: Owing to their tunable properties, controllable degradation, and ability to protect labile drugs, hydrogels are increasingly investigated as local drug delivery systems. However, a lack of standardized methodologies used to characterize and evaluate drug release poses significant difficulties when comparing findings from different investigations, preventing an accurate assessment of systems. Here, we review the commonly used analytical techniques for drug detection and quantification from hydrogel delivery systems. The experimental conditions of drug release in saline solutions and their impact are discussed, along with the main mathematical and statistical approaches to characterize drug release profiles. We also review methods to determine drug diffusion coefficients and in vitro and in vivo models used to assess drug release and efficacy with the goal to provide guidelines and harmonized practices when investigating novel hydrogel drug delivery systems.
142 citations
Cites background from "Wound pH-Responsive Sustained Relea..."
...systems were developed to have a minimal release at physiological pH and an accelerated release at acidic pH and wound healing pH [131,132]....
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...Consequently, smart hydrogel drug delivery systems were developed to have a minimal release at physiological pH and an accelerated release at acidic pH and wound healing pH [131,132]....
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TL;DR: The role of growth factors in tissue regeneration, and their application in both pre-clinical animal models of regeneration and clinical trials is discussed, and current status of biomaterial substrates and sophisticated delivery systems such as nanoparticles for delivery of exogenous growth factors and peptides in humans are reviewed.
Abstract: Growth factors are soluble secreted proteins capable of affecting a variety of cellular processes important for tissue regeneration. Consequently, the self-healing capacity of patients can be augmented by artificially enhancing one or more processes important for healing through the application of growth factors. However, their application in clinics remains limited due to lack of robust delivery systems and biomaterial carriers. Interestingly, all clinically approved therapies involving growth factors utilize some sort of a biomaterial carrier for growth factor delivery. This suggests that biomaterial delivery systems are extremely important for successful usage of growth factors in regenerative medicine. This review outlines the role of growth factors in tissue regeneration, and their application in both pre-clinical animal models of regeneration and clinical trials is discussed. Additionally, current status of biomaterial substrates and sophisticated delivery systems such as nanoparticles for delivery of exogenous growth factors and peptides in humans are reviewed. Finally, issues and possible future research directions for growth factor therapy in regenerative medicine are discussed.
117 citations
Cites background from "Wound pH-Responsive Sustained Relea..."
...The most commonly used stimuli for creating these systems are changes in temperature([94]) or pH([95]) or local enzymes such as proteases that are found in the injury site....
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TL;DR: A fundamental understanding of connective tissues and their multiscale properties are linked to better inform the design and translation of novel biomaterials to promote their regeneration.
Abstract: Connective tissue is one of the four major types of animal tissue and plays essential roles throughout the human body. Genetic factors, aging, and trauma all contribute to connective tissue dysfunction and motivate the need for strategies to promote healing and regeneration. The goal here is to link a fundamental understanding of connective tissues and their multiscale properties to better inform the design and translation of novel biomaterials to promote their regeneration. Major clinical problems in adipose tissue, cartilage, dermis, and tendon are discussed that inspire the need to replace native connective tissue with biomaterials. Then, multiscale structure-function relationships in native soft connective tissues that may be used to guide material design are detailed. Several biomaterials strategies to improve healing of these tissues that incorporate biologics and are biologic-free are reviewed. Finally, important guidance documents and standards (ASTM, FDA, and EMA) that are important to consider for translating new biomaterials into clinical practice are highligted.
116 citations
References
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TL;DR: In this article, the authors focused on temperature and pH responsive polymer systems and additionally the other stimuli-based responsive polymers will be assessed, which is more helpful to design new approaches because the basic concepts and mechanisms are systematically connected.
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TL;DR: This review highlights the use of hydrogels (a class of polymeric systems) in controlled drug delivery, and their application in stimuli- responsive, especially pH-responsive, drug release.
1,593 citations